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Ontogenetic Expression of Dopamine-Related Transcription Factors and Tyrosine Hydroxylase in Prenatally Stressed Rats

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Abstract

The development of the central nervous system can be permanently affected by insults received during the perinatal period, predisposing the organism to long-term behavioral and neurochemical abnormalities. Rats exposed to different types of stress during the last week of gestation produce offspring that show several alterations, many of which have been attributed to changes in dopamine (DA) neurotransmission that could serve as the neurochemical basis for the development of neuropsychiatric disorders. Employing an immunocytochemical approach, we studied the expression levels of two transcription factors Nurr1 and Pitx3 which are expressed at critical moments of DA neurons differentiation as well as the expression of the rate limiting enzyme in DA synthesis, tyrosine hydroxylase (TH) in mesencephalic areas of the brains of prenatally stressed (PS) offspring at different postnatal ages. Main results show that stress exerted to the gestant mother produces permanent effect in the ontogenetic expression of key factors related to the DA metabolism mainly in the ventral tegmental area (VTA) of the mesencephalon. The immunocytochemical expression of the transcription factor Nurr1 shows an increase at postnatal days (PNDs) 7, 28, and 60 whereas Pitx3 shows a decrease at PND 28 and an increase at 60 PND. The rate limiting step in DA synthesis, the enzyme TH shows a decrease at PND 7 to reach control levels at PNDs 28 and 60. The increase of TFs might be up-regulating TH in order to restore DA levels that were previously seen to be normal before puberty. The area selectivity of the increase of the TFs toward VTA and the mesolimbic pathway indicates that an insult received during the prenatal period will exert mainly motivational, emotional, and reward behavior impairments in the adult life.

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Acknowledgments

We are greatly indebted to Dr. Marten Smidt (Utrecht University, The Netherlands) for the gift of Pitx3 antibody. We thank Dr. Carlos J. Baier for his help in preparing the figures and for critical reading of the manuscript and helpful discussions. We appreciate the help of Dr. Alberto J. Ramos in the image analysis of the data. The skillful technical assistance and bibliographical management of Mrs. Susana Buglione is greatly appreciated. This research was supported by grants from CONICET (PIP 6015) and ANPCYT (PICT 31981) (to MCA) and UBACYT M004 (to AB).

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  1. Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina

    Maria R. Katunar & Marta C. Antonelli

  2. Instituto de Biología Celular y Neurociencia (UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    Trinidad Saez & Alicia Brusco

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  1. Maria R. Katunar
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  2. Trinidad Saez
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Correspondence to Marta C. Antonelli.

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Katunar, M.R., Saez, T., Brusco, A. et al. Ontogenetic Expression of Dopamine-Related Transcription Factors and Tyrosine Hydroxylase in Prenatally Stressed Rats. Neurotox Res 18, 69–81 (2010). https://doi.org/10.1007/s12640-009-9132-z

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